CN116463300A - Production and purification process and application of canine parvovirus - Google Patents
Production and purification process and application of canine parvovirus Download PDFInfo
- Publication number
- CN116463300A CN116463300A CN202310238813.3A CN202310238813A CN116463300A CN 116463300 A CN116463300 A CN 116463300A CN 202310238813 A CN202310238813 A CN 202310238813A CN 116463300 A CN116463300 A CN 116463300A
- Authority
- CN
- China
- Prior art keywords
- purification
- purification process
- canine parvovirus
- buffer
- production
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000746 purification Methods 0.000 title claims abstract description 62
- 241000701931 Canine parvovirus Species 0.000 title claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 23
- 239000012535 impurity Substances 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000012856 packing Methods 0.000 claims abstract description 14
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 150000001450 anions Chemical class 0.000 claims abstract description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 21
- 239000000945 filler Substances 0.000 claims description 21
- 239000000872 buffer Substances 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims description 8
- 238000010828 elution Methods 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 3
- 238000009776 industrial production Methods 0.000 claims description 3
- 125000000129 anionic group Chemical group 0.000 claims description 2
- 238000005352 clarification Methods 0.000 claims 1
- 238000005498 polishing Methods 0.000 claims 1
- 241000700605 Viruses Species 0.000 abstract description 23
- 231100000419 toxicity Toxicity 0.000 abstract description 16
- 230000001988 toxicity Effects 0.000 abstract description 16
- 239000007788 liquid Substances 0.000 abstract description 12
- 230000003321 amplification Effects 0.000 abstract description 3
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 3
- 239000004801 Chlorinated PVC Substances 0.000 description 25
- 229920000457 chlorinated polyvinyl chloride Polymers 0.000 description 25
- 239000007853 buffer solution Substances 0.000 description 10
- 239000002808 molecular sieve Substances 0.000 description 9
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 238000000108 ultra-filtration Methods 0.000 description 3
- 206010017472 Fumbling Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012527 feed solution Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000013622 capto Q Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940028617 conventional vaccine Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14311—Parvovirus, e.g. minute virus of mice
- C12N2750/14351—Methods of production or purification of viral material
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a production and purification process and application of canine parvovirus, wherein the purification process is used for filtering and clarifying a canine parvovirus culture, then carrying out crude purification and concentration by using anion column packing, and then carrying out fine purification by using packing Core400 to obtain purified canine parvovirus; the purification process ensures that the impurity removal rate reaches 98% under the condition of ensuring no loss of the toxicity; the virus yield of the whole process reaches 100%, the requirement of capacity amplification in production is met, the production efficiency is improved, and the purification of CPV feed liquid of GMP grade hundred-upgrade in workshops can be realized.
Description
Technical Field
The invention relates to the technical field of virus purification, in particular to a canine parvovirus production and purification process and application.
Background
Canine parvovirus (CPV, canine Parvovirus) has strong resistance to various physical and chemical factors and common disinfectants, mainly infects puppies, and is extremely infectious and extremely lethal. The improvement of the whole virus purification process for canine parvovirus is one of important means for improving the effectiveness and safety of canine parvovirus vaccine, namely improving the CPV (chlorinated polyvinyl chloride) valence and purity level. The high-quality purification process meets the requirements of toxic price seedling preparation and purity, and also needs to achieve high yield and production efficiency, such as improving batch processing capacity, shortening purification time and the like.
At present, CPV has no documents and patent reports of purification process, most of all-virus conventional purification processes are applied to CPV, and have the problems of low yield, low batch processing amount and the like, so that the effectiveness of products and the control of production cost cannot be ensured, and meanwhile, due to the characteristics of the pet product market, the CPV purification process meets the double requirements of high quality and cost control of the products so as to ensure good market response and profit.
Disclosure of Invention
In view of the above, the invention provides a canine parvovirus production and purification process, which realizes crude purity and fine purity by selecting the combination of various chromatographic fillers, and solves the defects existing in the purification process in the prior art so as to meet the industrial scale-up production and market demands.
Based on the above, the technical scheme of the invention is as follows:
a process for preparing and purifying the canine parvovirus includes such steps as filtering, clarifying, concentrating, eluting, collecting virus, and refining by Core 400.
Preferably, in the steps of crude purification and concentration, a first buffer is added to the anionic column packing to maintain the conductivity of the packing at 3-7 mS/cm and the pH at 7.5-7.8, and then a second buffer is used to remove protein impurities.
Further, the first buffer is50mM Tris-HCl pH 7.5; the second buffer was 50mM Tris-HCl150mM NaClpH 7.5.
Preferably, the elution process employs a third buffer: 50mM Tris-HCl 500mM NaCl pH7.5.
Further, the fine purification step uses a fourth buffer to maintain the conductivity of the filler at 8-12 mS/cm and pH 7.5-7.8.
Preferably, the fourth buffer is50mM Tris50mM NaCl.
Further, the filtering and clarifying process adopts a 0.65 μm capsule type filter element.
Further, the canine parvovirus has an increased titer after purification relative to prior to purification.
The invention also provides application of the purification process in industrial production of canine parvovirus, the purification process can completely meet the requirements of industrial production, and high-quality purified viruses are obtained.
The invention has the beneficial effects that:
1. the purification process provided by the invention has high treatment efficiency, and the impurity removal rate reaches 98% under the condition of ensuring that the toxicity is not lost; the virus yield of the whole process reaches 100 percent.
2. The purification process provided by the invention can meet the requirement of capacity amplification in production, improves the production efficiency, can realize the purification of CPV feed liquid in a workshop GMP level hundred-upgrade, and ensures the effectiveness of the product and the control of the production cost.
Drawings
FIG. 1 is a graph of the CPV virus of the present invention after crude and fine purification, respectively.
FIG. 2 is a graph of the CPV plant of the present invention after hundred liter stages of rough purity and refined purity.
FIG. 3 shows the results of chromatography of CPV virus according to the present invention using a thousand pure 4FF molecular sieve.
FIG. 4 shows the analysis results of CPV virus according to the present invention by using Boglycopyrrolate 4FF molecular sieve.
FIG. 5 shows the results of purification and upgrade production chromatography of CPV virus according to the present invention using conventional techniques.
Detailed Description
The following description of the technical solutions in the embodiments of the present invention will be clear and complete, and it is obvious that the described embodiments are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
In an embodiment of the invention, a canine parvovirus production and purification process is provided, which comprises the following steps: filtering and clarifying the canine parvovirus culture, purifying and concentrating the canine parvovirus culture by using an anion column filler NanoGel 50Q, eluting and collecting viruses, and purifying by using a filler Core400 to obtain the purified canine parvovirus.
In an embodiment of the present invention, specifically, the purification process is: firstly, carrying out balancing 50Q operation by using a first buffer system, so that the filler is kept at a conductivity of about 3-7 mS/cm and a pH value of about 7.5-7.8 to achieve balancing; after 50Q balancing, filtering and clarifying canine parvovirus feed liquid by using a 0.65 mu m capsule filter element, and carrying out sample loading operation, wherein the volume of a sample loading column is about 20 CV-30 CV; washing the mixed protein with a second buffer system for at least 5 column volumes; eluting CPV virus particles by a third buffer system, and collecting eluted virus; balancing Core400 filler with a fourth buffer to maintain the filler at a conductivity of about 8-12 mS/cm and at a pH of about 7.5-7.8; and (3) passing the eluted virus through the Core400, and collecting the flow-through liquid, namely the refined virus liquid.
As a preferred embodiment, the first buffer is50mM Tris-HCl pH 7.5; the second buffer was 50mM Tris-HCl150mM NaCl pH7.5. The elution process uses a third buffer: 50mM Tris-HCl 500mM NaClpH 7.5. The fourth buffer solution is used for maintaining the conductivity of the filling material to be 8-12 mS/cm and the pH value to be 7.5-7.8 in the fine purification step. The fourth buffer is50mM Tris50mM NaCl. Under the experimental conditions, the virus valence is not lost, the virus yield reaches 100%, the impurity removal rate reaches more than 98%, and the detection gel diagram shows that no obvious impurity protein band exists.
In the scheme, the CPV particle size is too small, so that the loss in the traditional ultrafiltration membrane bag concentration process and the traditional molecular sieve purification process is too large, and the efficiency of the old process is greatly reduced. General purpose medicineCPV is primarily purified by anion chromatography 50Q filling, and the purposes of 10-30 times concentration and primary impurity protein removal can be achieved. Can be used for preparing a drug with a toxicity of 6.5TCID 50 0.1mL canine parvovirus culture was promoted to CPV 7.5TCID 50 0.1mL of seedling preparation requirement; after that, the Core400 filler is refined, so that the new process flow with the impurity removal rate of 98% is ensured under the condition of no loss of the toxicity; the virus yield of the whole process reaches 100%, the requirement of capacity amplification in production is met, the labor time is shortened, and the purification of CPV feed liquid of GMP grade hundred-upgrade in workshops can be realized.
Examples
Culture scheme for CPV feed solution: culturing well-grown F81 cells (supplied by Kogyo Co., ltd.) as monolayer, discarding the growth solution, digesting the cells, and mixing the cell suspension with the culture medium according to 3.010 5 Inoculating the cells per ml to a reactor, the carrier dosage is 2-5 g/L, setting the parameters of the reactor (the temperature is 37 ℃, the dissolved oxygen is 45-60%, the PH value is 7.2-7.3), and inoculating the canine parvovirus seed virus for the conventional vaccine according to the proportion of 2% of the maintenance solution after the cells grow to be full of a single layer. Harvesting virus liquid when about 80% cytopathy appears, and storing at-20deg.C;
fumbling of cpv concentration conditions: selecting an ultrafiltration concentration membrane package of the Kebaite company, a NanoGel 50Q filler of the NanoGel company and a CaptoQ filler of the Cytiva company as a screening scheme; the result of the concentrated film package scheme of the Kebaite company shows that the process has larger loss of the toxicity and the toxicity is from 6.5TCID 50 0.1mL down to 4.0TCID 50 The filler of/0.1mL,Cytiva Capto Q has a toxicity value of 6.5TCID 50 0.1mL down to 5.5TCID 50 0.1mL, the loss of the toxicity of both schemes is larger; only NanoGel 50Q filler can achieve the effect of improving concentrated toxicity, i.e. the toxicity is 6.5TCID 50 0.1mL was raised to 7.5TCID 50 /0.1mL；
3. Optimization of the refinement scheme: comparing the purifying effects of Bognon and 4FF molecular sieve filler of Qian pure company and composite filler of Cytiva company, the results show that the impurity removal rate of the molecular sieve filler of two companies reaches 98% after purification, but the toxic price loss is larger, the requirements are not met, and only Core400 of Cytiva company meets the double requirements of 98% of impurity removal rate and no toxic price loss;
4.50 selection of a chromatography buffer system: according to the linear elution, the first buffer system was chosen: 50mM Tris-HCl pH7.5 as the equilibrium salt of 50Q filler; second buffer system: 50mM Tris-HCl150mM NaCl pH7.5 as the impurity washing liquid; third buffer system: 50mM Tris-HCl 500mM NaCl pH7.5 as virus eluent; under the experimental condition, the virus yield reaches 100%, the impurity removal rate reaches more than 98%, and the gel diagram detection has no obvious impurity protein band;
5. fumbling 50Q elution condition range: further searching the elution range, defining the range of chromatographic parameters to control the operable space in the production process, and performing experimental optimization according to DoE (Design ofExperiments) tools to determine that the pH range of the eluent in the chromatographic step is 7.5-7.8, the pH is lower than 7.5, so that the toxicity is lost, and the pH is higher than 7.8 and does not meet the seedling preparation standard; the electric conductivity range of the eluent is 18.7-19.7 mS/cm; the loss of the toxicity is larger when the conductance is higher than the range, and the impurity removal efficiency is reduced when the conductance is lower than the range;
core400 chromatography buffer system: according to the general buffer of the filler, a fourth buffer system: 50mM Tris50mM NaCl as a balanced salt of Core400 filler.
Experimental example 1 laboratory purification process validation on different scales
Using the CPV broth described in the examples, we completed 3 scale process runs in the laboratory, following the process futured in the examples, respectively:
1) Purification of 100mL of CPV feed was accomplished with 5mL of 50q filler and 5mL of Core400 filler;
2) Purification of 1000mL of CPV feed solution was accomplished with 50mL of 50Q packing and 5mL of Core400 packing;
3) Purifying 10-19L CPV feed liquid by 500mL of 50Q packing and 100mL of Core400 packing;
the results of the CPV impurity removal rate and yield data obtained by the purification of the virus after the crude purification and the fine purification are shown in Table 1. The purification gel is shown in FIG. 1.
Table 1:
the results in table 1 show that: CPV toxicity after purification is improved relative to culture solution toxicity, and is higher than 7.5, the overall impurity removal rate is higher than 98%, the yield is 100%, and no obvious impurity protein trace exists after purification in figure 1.
Experimental example 2 workshop hundred upgrade purification process verification
In a GMP plant, testing of batches of 50-100L of feed liquid as shown in Table 2 was completed using 8.5L of 50Q packing and 3.5L of Core400 packing; the results obtained were: the impurity removal rate is more than 98%, and the yield can be 100%. Taking 126L specification production as an example, the purification gel diagram is shown in FIG. 2, and no obvious trace of protein impurities is found after the purification.
Table 2:
comparison experiment: comparison of purification effects of traditional Process
Concentrating CPV feed liquid prepared in the embodiment by 30 times by using an ultrafiltration membrane bag, then passing through a 4FF molecular sieve, detecting the purity and the toxicity of each collected component, and calculating the impurity removal rate and the final yield; experimental data show that the purity of CPV feed liquid which is concentrated by 30 times and is 4FF molecular sieve types (Qian-pure Bo-Gu) of two companies reaches the standard, no obvious impurity protein exists, the impurity removal rate is more than 98%, but the yield is 6.2% and 2.6% respectively; the experimental data of hundred-liter production are the same, the impurity removal rate reaches the standard, no obvious impurity protein strips exist, and the yield is only 1.5%.
1. The analysis with thousand pure 4FF molecular sieves is shown in table 3 and the results are shown in figure 3.
Table 3:
| as is | E1 | E2 | E1+E2 | |
| Concentration (mg/mL) | 6.585 | 0.275 | 0.283 | 0.279 |
| LgTCID 50 (0.1mL) | 7.3 | 4.43 | 6 | - |
| Volume (mL) | 10 | 16 | 12 | 28 |
Wherein, E1: purifying the peak; e2: a plateau peak; e3: pigment peaks; e1+e2: samples were harvested.
2. The conditions of the molecular sieve chromatography using Boglycopyrrolate 4FF are shown in Table 4, and the results of the chromatography are shown in FIG. 4.
Table 4:
wherein, E1: purifying the peak; e2: a plateau peak; e3: pigment peaks; e4, pigment tail; e1+e2: samples were harvested.
3. Hundred liter production experimental data
The toxicity results obtained in hundred-upgrade production experiments are shown in Table 5, and the chromatographic results are shown in FIG. 5.
Table 5:
finally, although the invention has been described in detail in the foregoing general description and specific examples, the foregoing examples are illustrative only and not limiting of the invention; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (9)
1. A production and purification process for canine parvovirus is characterized in that canine parvovirus culture is filtered, clarified, subjected to anion column packing NanoGel 50Q rough purification and concentration, eluted and collected, and subjected to fine purification by a packing Core400 to obtain purified canine parvovirus.
2. The purification process according to claim 1, wherein in the crude purification and concentration steps, a first buffer is added to the anionic column packing to maintain the conductivity of the packing at 3 to 7mS/cm and the pH at 7.5 to 7.8, and then a second buffer is used to remove protein impurities.
3. The purification process of claim 2, wherein the first buffer is50mM Tris-HCl pH 7.5; the second buffer was 50mM Tris-HCl150mM NaCl pH7.5.
4. The purification process of claim 1, wherein the elution process employs a third buffer: 50mM Tris-HCl 500mM NaCl pH7.5.
5. The purification process according to claim 1, wherein the polishing step uses a fourth buffer to maintain the conductivity of the filler at 8-12 mS/cm, pH 7.5-7.8.
6. The purification process of claim 5, wherein the fourth buffer is50mM Tris50mM NaCl.
7. The purification process of claim 1, wherein the filtration clarification process employs a 0.65 μm capsule filter.
8. The purification process of claim 1, wherein the canine parvovirus has an increased titer after purification relative to prior to purification.
9. Use of the purification process of any one of claims 1-8 in the industrial production of canine parvovirus.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310238813.3A CN116463300A (en) | 2023-03-07 | 2023-03-07 | Production and purification process and application of canine parvovirus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310238813.3A CN116463300A (en) | 2023-03-07 | 2023-03-07 | Production and purification process and application of canine parvovirus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116463300A true CN116463300A (en) | 2023-07-21 |
Family
ID=87176137
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310238813.3A Pending CN116463300A (en) | 2023-03-07 | 2023-03-07 | Production and purification process and application of canine parvovirus |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116463300A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117106732A (en) * | 2023-09-07 | 2023-11-24 | 华中农业大学 | Canine parvovirus and application thereof |
-
2023
- 2023-03-07 CN CN202310238813.3A patent/CN116463300A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117106732A (en) * | 2023-09-07 | 2023-11-24 | 华中农业大学 | Canine parvovirus and application thereof |
| CN117106732B (en) * | 2023-09-07 | 2024-02-06 | 华中农业大学 | Canine parvovirus and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2134360B1 (en) | Virus like particle purification | |
| CN116463300A (en) | Production and purification process and application of canine parvovirus | |
| CN112279919A (en) | Preparation method of anti-PD-1 antibody | |
| CN102584934A (en) | Process for preparing human immunoglobulin for intravenous injection | |
| CN110241093A (en) | A kind of purification process of recombinant poxvirus | |
| CN114181300A (en) | Preparation method of high-purity monoclonal antibody | |
| US4743551A (en) | Purification of microbial rennet from Mucor miehei | |
| CN104710527B (en) | A kind of endotoxin removal method of biological products | |
| CN111171117B (en) | Purification process of recombinant CA16 virus-like particles, recombinant CA16 virus vaccine and preparation method thereof | |
| JP2023145471A (en) | In-line product concentration to reduce volumetric load flow rate and increase productivity of bind and elute chromatography purification | |
| CN115286716B (en) | Method for large-scale purification of anti-PD-1 antibody | |
| EP3896163A1 (en) | Method for separating and purifying recombinant human fibronectin from genetically engineered rice seed | |
| CN114106114B (en) | Method for purifying foot-and-mouth disease virus antigen by utilizing ion exchange chromatography | |
| CN108101982A (en) | A kind of purification process of monoclonal antibody | |
| WO2023031858A1 (en) | Plasmid dna purification methods | |
| Metzger et al. | Evaluating adsorptive filtration as a unit operation for virus removal | |
| CN103642794B (en) | A kind of a large amount of methods for preparing BCG-CpG-DNA | |
| CN1250567C (en) | Method of purifying calcium ion-binding protein | |
| CN115779683B (en) | Virus-removing filtering method | |
| CN111172048A (en) | Coarse and pure process of CA16 virus-like particles expressed by recombinant hansenula polymorpha, CA16 virus vaccine and preparation method thereof | |
| CN114164204A (en) | Method for purifying plasmid | |
| CN104693303B (en) | A kind of nucleic acid minimizing technology in protein product | |
| CN115894604B (en) | Recombinant protein clarifying and purifying method | |
| CN111848784B (en) | Separation and purification method of high-concentration intravenous injection human immunoglobulin | |
| CN116375872A (en) | Method for purifying ROR1 monoclonal antibody |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |